Increasing evidence suggests that the dopamine transporter is an important window on pathological changes that occur in dopamine neurons. In Parkinson's diseased brains, [3H] WIN 35,428 was the first marker to detect losses that corresponded to the reported reduction of dopamine in this brain region (Madras et al., 1990, Kaufman and Madras, 1991). PET and SPECT imaging with phenyltropane analogs have corroborated our in vitro findings. We developed a SPECT imaging agent, [123I] altropane (N-iodoallyl-2 carbomethoxy-3 -(4-fluorophenyl)tropane) that displays transporter selectivity and brain imaging properties in nonhuman primates particularly suitable for this application (Elmaleh et al., in press, Madras et al., 1994, Fischman et al., 1995). [125I]Altropane is effective in detecting Parkinson's disease in post-mortem tissues. In normal human putamen, [125I] altropane binds to the dopamine transporter with high affinity (Kd 4.96 q 0.38 nM; n=4), a low level of nonspecific binding, an appropriate pharmacology for the dopamine transporter (r=0.98; p < .001), and site density (212 q 41.1 pmol/g). In Parkinson's diseased putamen, matched for age and post-mortem interval, the density was reduced by 90%. Altropane is a promising SPECT imaging agent for monitoring Parkinson's disease. SPECT imaging studies